tbuckley/cabot-search huggingface dataset:
Abstract A002: Genetic and immune landscape evolution defines subtypes of MMR deficient colorectal cancer
Authors: Benjamin R. Challoner, Andrew Woolston, David Lau, Marta Buzzetti, Louise J. Barber, Tom Lund, Harold B. Sansano, Katharina von Loga, Héctor Lázare-Iglesias, Ruwaida Begum, Richard Crux, David Cunningham, Ian Chau, Naureen Starling, Juan Ruiz-Bañobre, Tony Dhillon, Marco Gerlinger
Journal: Cancer Research (2022)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR012) of the Conference Proceedings. Citation Format: Benjamin R. Challoner, Andrew Woolston, David Lau, Marta Buzzetti, Louise J. Barber, Tom Lund, Harold B. Sansano, Katharina von Loga, Héctor Lázare-Iglesias, Ruwaida Begum, Richard Crux, David Cunningham, Ian Chau, Naureen Starling, Juan Ruiz-Bañobre, Tony Dhillon, Marco Gerlinger. Genetic and immune landscape evolution defines subtypes of MMR deficient colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A002.
Over-the-scope clips versus standard treatment
Authors: Alan N Barkun, Loren Laine, Grigorios I Leontiadis, John R Saltzman
Journal: Gut (2022)

Drugs targeting the orphan receptor GPR35 have potential therapeutic application in a number of disease areas, including inflammation, metabolic disorders, nociception, and cardiovascular disease. Currently available surrogate GPR35 agonists identified from pharmacologically relevant compound libraries have limited utility due to the likelihood of off-target effects in vitro and in vivo and the variable potency that such ligands exhibit across species. We sought to identify and characterize novel GPR35 agonists to facilitate studies aimed at defining the physiologic role of GPR35. PathHunter <i>β</i>-arrestin recruitment technology was validated as a human GPR35 screening assay, and a high-throughput screen of 100,000 diverse low molecular weight compounds was conducted. Confirmed GPR35 agonists from five distinct chemotypes were selected for detailed characterization using both <i>β</i>-arrestin recruitment and G protein-dependent assays and each of the human, mouse, and rat GPR35 orthologs. These studies identified 4-{(Z)-[(2Z)-2-(2-fluorobenzylidene)-4-oxo-1,3-thiazolidin-5-ylidene]methyl}benzoic acid (compound 1) as the highest potency full agonist of human GPR35 yet described. As with certain other GPR35 agonists, compound 1 was markedly selective for human GPR35, but displayed elements of signal bias between <i>β</i>-arrestin-2 and G protein-dependent assays. Compound 1 also displayed competitive behavior when assessed against the human GPR35 antagonist, ML-145 (2-hydroxy-4-[4-(5<i>Z</i>)-5-[(<i>E</i>)-2-methyl-3-phenylprop-2-enylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]butanoylamino]benzoic acid). Of the other chemotypes studied, compounds 2 and 3 were selective for the human receptor, but compounds 4 and 5 demonstrated similar activity at human, rat, and mouse GPR35 orthologs. Further characterization of these compounds and related analogs is likely to facilitate a better understanding of GPR35 in health and disease.
Trial of a Preferential Phosphodiesterase 4B Inhibitor for Idiopathic Pulmonary Fibrosis
Authors: Luca Richeldi, Arata Azuma, Vincent Cottin, Christian Hesslinger, Susanne Stowasser, Claudia Valenzuela, Marlies S. Wijsenbeek, Donald F. Zoz, Florian Voss, Toby M. Maher
Journal: New England Journal of Medicine (2022)

Phosphodiesterase 4 (PDE4) inhibition is associated with antiinflammatory and antifibrotic effects that may be beneficial in patients with idiopathic pulmonary fibrosis.In this phase 2, double-blind, placebo-controlled trial, we investigated the efficacy and safety of BI 1015550, an oral preferential inhibitor of the PDE4B subtype, in patients with idiopathic pulmonary fibrosis. Patients were randomly assigned in a 2:1 ratio to receive BI 1015550 at a dose of 18 mg twice daily or placebo. The primary end point was the change from baseline in the forced vital capacity (FVC) at 12 weeks, which we analyzed with a Bayesian approach separately according to background nonuse or use of an antifibrotic agent.A total of 147 patients were randomly assigned to receive BI 1015550 or placebo. Among patients without background antifibrotic use, the median change in the FVC was 5.7 ml (95% credible interval, -39.1 to 50.5) in the BI 1015550 group and -81.7 ml (95% credible interval, -133.5 to -44.8) in the placebo group (median difference, 88.4 ml; 95% credible interval, 29.5 to 154.2; probability that BI 1015550 was superior to placebo, 0.998). Among patients with background antifibrotic use, the median change in the FVC was 2.7 ml (95% credible interval, -32.8 to 38.2) in the BI 1015550 group and -59.2 ml (95% credible interval, -111.8 to -17.9) in the placebo group (median difference, 62.4 ml; 95% credible interval, 6.3 to 125.5; probability that BI 1015550 was superior to placebo, 0.986). A mixed model with repeated measures analysis provided results that were consistent with those of the Bayesian analysis. The most frequent adverse event was diarrhea. A total of 13 patients discontinued BI 1015550 treatment owing to adverse events. The percentages of patients with serious adverse events or severe adverse events were similar in the two trial groups.In this placebo-controlled trial, treatment with BI 1015550, either alone or with background use of an antifibrotic agent, prevented a decrease in lung function in patients with idiopathic pulmonary fibrosis. (Funded by Boehringer Ingelheim; 1305-0013 ClinicalTrials.gov number, NCT04419506.).
The effect of diabetes and prediabetes on the prevalence, complications and mortality in nonalcoholic fatty liver disease
Authors: Cheng Han Ng, Kai En Chan, Yip Han Chin, Rebecca Wenling Zeng, Pei Chen Tsai, Wen Hui Lim, Darren Jun Hao Tan, Chin Meng Khoo, Lay Hoon Goh, Zheng Jye Ling, Anand Kulkarni, Lung-Yi Loey Mak, Daniel Q Huang, Mark Chan, Nicholas WS Chew, Mohammad Shadab Siddiqui, Arun J. Sanyal, Mark Muthiah
Journal: Clinical and Molecular Hepatology (2022)

Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals.Data from the National Health and Nutrition Examination Survey 1999-2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk.Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality.Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.
Chitosan@Puerarin hydrogel for accelerated wound healing in diabetic subjects by miR-29ab1 mediated inflammatory axis suppression
Authors: Xiaoling Zeng, Baohui Chen, Luping Wang, Yingxiao Sun, Zhao Jin, Xuanyong Liu, Liping Ouyang, Yun Liao
Journal: Bioactive Materials (2022)

Wound healing is one of the major global health concerns in patients with diabetes. Overactivation of pro-inflammatory M1 macrophages is associated with delayed wound healing in diabetes. miR-29ab1 plays a critical role in diabetes-related macrophage inflammation. Hence, inhibition of inflammation and regulation of miR-29 expression have been implicated as new points for skin wound healing. In this study, the traditional Chinese medicine, puerarin, was introduced to construct an injectable and self-healing chitosan@puerarin (C@P) hydrogel. The C@P hydrogel promoted diabetic wound healing and accelerated angiogenesis, which were related to the inhibition of the miR-29 mediated inflammation response. Compared to healthy subjects, miR-29a and miR-29b1 were ectopically increased in the skin wound of the diabetic model, accompanied by upregulated M1-polarization, and elevated levels of IL-1β and TNF-α. Further evaluations by miR-29ab1 knockout mice exhibited superior wound healing and attenuated inflammation. The present results suggested that miR-29ab1 is essential for diabetic wound healing by regulating the inflammatory response. Suppression of miR-29ab1 by the C@P hydrogel has the potential for improving medical approaches for wound repair.
Patient-Reported Outcome Measures—Challenges and Opportunities for China
Authors: Donald E. Casey
Journal: JAMA Network Open (2022)

Hui Zhou, MSc; Mi Yao, MD; Xiaodan Gu, MBBS; Mingrui Liu, BP; Ruifeng Zeng, MBBS; Qin Li, MNS; Tingjia Chen, MD; Wen He, MD; Xiao Chen, PhD; Gang Yuan, MD, PhD
Moderate Hypothermia vs Normothermia and 30-Day Mortality in Patients With Cardiogenic Shock Receiving Venoarterial ECMO
Authors: Federico Pappalardo, Andrea Montisci
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Suicide Risk Prediction in Clinical Settings—Additional Considerations for Face-to-Face Screening and Machine Learning Approaches
Authors: Jordan E. DeVylder
Journal: JAMA Network Open (2022)

Drew Wilimitis, BS; Robert W. Turer, MD, MS; Michael Ripperger, BE; Allison B. McCoy, PhD; Sarah H. Sperry, PhD; Elliot M. Fielstein, PhD; Troy Kurz, MD; Colin G. Walsh, MD, MA
Apoptotic vesicles activate autophagy in recipient cells to induce angiogenesis and dental pulp regeneration
Authors: Zihan Li, Meiling Wu, Siying Liu, Xuemei Liu, Yu Huan, Qingyuan Ye, Xiaoxue Yang, Hao Guo, Anqi Liu, Xiaoyao Huang, Xiaoshan Yang, Feng Ding, Haokun Xu, Jun Zhou, Peisheng Liu, Shiyu Liu, Yan Jin, Kun Xuan
Journal: Molecular Therapy (2022)

Extracellular vesicles (EVs) derived from living cells play important roles in donor cell-induced recipient tissue regeneration. Although numerous studies have found that cells undergo apoptosis after implantation in an ischemic-hypoxic environment, the roles played by the EVs released by apoptotic cells are largely unknown. In this study, we obtained apoptotic vesicles (apoVs) derived from human deciduous pulp stem cells and explored their effects on the dental pulp regeneration process. Our work showed that apoVs were ingested by endothelial cells (ECs) and elevated the expression of angiogenesis-related genes, leading to pulp revascularization and tissue regeneration. Furthermore, we found that, at the molecular level, apoV-carried mitochondrial Tu translation elongation factor was transported and regulated the angiogenic activation of ECs via the transcription factor EB-autophagy pathway. In a beagle model of dental pulp regeneration in situ, apoVs recruited endogenous ECs and facilitated the formation of dental-pulp-like tissue rich in blood vessels. These findings revealed the significance of apoptosis in tissue regeneration and demonstrated the potential of using apoVs to promote angiogenesis in clinical applications.
The need for increased pragmatism in cardiovascular clinical trials
Authors: Muhammad Shariq Usman, Harriette G. C. Van Spall, Stephen J. Greene, Ambarish Pandey, Darren K. McGuire, Ziad A. Ali, Robert J. Mentz, Gregg C. Fonarow, John A. Spertus, Stefan D. Anker, Javed Butler, Stefan K. James, Muhammad Shahzeb Khan
Journal: Nature Reviews Cardiology (2022)
Abstract A017: In vivo tracking of clonal dynamics during UV-induced skin carcinogenesis
Authors: Stanislav Avdieiev, Leticia Tordesillas, Omar Chavez Chiang, Zhihua Chen, Luiza Silva Simoes, Y. Ann Chen, Noemi Andor, Robert Gatenby, Elsa R. Flores, Joel S. Brown, Kenneth Y. Tsai
Journal: Cancer Research (2022)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Proffered Abstracts section (PR004) of the Conference Proceedings. Citation Format: Stanislav Avdieiev, Leticia Tordesillas, Omar Chavez Chiang, Zhihua Chen, Luiza Silva Simoes, Y. Ann Chen, Noemi Andor, Robert Gatenby, Elsa R. Flores, Joel S. Brown, Kenneth Y. Tsai. In vivo tracking of clonal dynamics during UV-induced skin carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A017.
Repeated exposure to heterologous hepatitis C viruses associates with enhanced neutralizing antibody breadth and potency
Authors: Nicole Frumento, Alexis Figueroa, Tingchang Wang, Muhammad N. Zahid, Shuyi Wang, Guido Massaccesi, Georgia Stavrakis, James E. Crowe, Andrew I. Flyak, Hongkai Ji, Stuart C. Ray, George M. Shaw, Andrea L. Cox, Justin R. Bailey
Journal: Journal of Clinical Investigation (2022)

A prophylactic hepatitis C virus (HCV) vaccine that elicits neutralizing antibodies could be key to HCV eradication. However, the genetic and antigenic properties of HCV envelope (E1E2) proteins capable of inducing anti-HCV broadly neutralizing antibodies (bNAbs) in humans have not been defined. Here, we investigated the development of bNAbs in longitudinal plasma of HCV-infected persons with persistent infection or spontaneous clearance of multiple reinfections. By measuring plasma antibody neutralization of a heterologous virus panel, we found that the breadth and potency of the antibody response increased upon exposure to multiple genetically distinct infections and with longer duration of viremia. Greater genetic divergence between infecting strains was not associated with enhanced neutralizing breadth. Rather, repeated exposure to antigenically related, antibody-sensitive E1E2s was associated with potent bNAb induction. These data reveal that a prime-boost vaccine strategy with genetically distinct, antibody-sensitive viruses is a promising approach to inducing potent bNAbs in humans.
The Importance of Hair in Black−White Race Relations
Authors: Tosen Nwadei, Loren D. Krueger
Journal: JAMA Dermatology (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Long-term antibiotic exposure promotes mortality after systemic fungal infection by driving lymphocyte dysfunction and systemic escape of commensal bacteria
Authors: Rebecca A. Drummond, Jigar V. Desai, Emily E. Ricotta, Muthulekha Swamydas, Clay Deming, Sean Conlan, Mariam Quinones, Veronika Matei-Rascu, Lozan Sheriff, David Lecky, Chyi-Chia R. Lee, Nathaniel M. Green, Nicholas Collins, Adrian M. Zelazny, D. Rebecca Prevots, David Bending, David Withers, Yasmine Belkaid, Julia A. Segre, Michail S. Lionakis
Journal: Cell Host & Microbe (2022)
A call for de-implementation research and clinical practice in Chinese healthcare
Authors: Junqiang Zhao, Shelly-Anne Li, Ian D Graham, Senior Scientist
Journal: BMJ (2022)

Medical overuse in China and de-implementationIn recent years, The BMJ has published a series of articles highlighting medical overuse in China. 1 -5 Overdiagnosis and overtreatment increases the risk of adverse health outcomes, wastes scarce healthcare resources, increases healthcare spending for patients, disrupts the optimal allocation of medical resources, and increases staff workloads.De-implementation, defined as the "process of identifying and removing harmful, non-cost-effective, or ineffective practices based on tradition and without adequate scientific support" has emerged as a distinct research focus. 6 De-implementation research involves two main components: (a) investigating how to stop practices that are no longer supported by the evidence, or where the evidence has evolved, and (b) identifying strategies and processes for doing this.Disentangling these components can contribute to a knowledge base of how de-implementation might operate and provide a foundation for efficient and effective de-implementation practice.De-implementation of ineffective practices and procedures are actively promoted within the Choosing Wisely campaign, which was launched in the United States in 2012, and now spans over 20 countries worldwide.The campaign aims to engage healthcare providers and patients in conversations about unnecessary tests, treatments, and procedures. 7 Although the Choosing Wisely campaign has not been rolled out in China, there are principles that it could adopt.
Acute lymphoblastic leukemia displays a distinct highly methylated genome
Authors: Sara Hetzel, Alexandra L. Mattei, Helene Kretzmer, Chunxu Qu, Xiang Chen, Yiping Fan, Gang Wu, Kathryn G. Roberts, Selina Luger, Mark Litzow, Jacob Rowe, Elisabeth Paietta, Wendy Stock, Elaine R. Mardis, Richard K. Wilson, James R. Downing, Charles G. Mullighan, Alexander Meissner
Journal: Nature Cancer (2022)

Abstract DNA methylation is tightly regulated during development and is stably maintained in healthy cells. In contrast, cancer cells are commonly characterized by a global loss of DNA methylation co-occurring with CpG island hypermethylation. In acute lymphoblastic leukemia (ALL), the commonest childhood cancer, perturbations of CpG methylation have been reported to be associated with genetic disease subtype and outcome, but data from large cohorts at a genome-wide scale are lacking. Here, we performed whole-genome bisulfite sequencing across ALL subtypes, leukemia cell lines and healthy hematopoietic cells, and show that unlike most cancers, ALL samples exhibit CpG island hypermethylation but minimal global loss of methylation. This was most pronounced in T cell ALL and accompanied by an exceptionally broad range of hypermethylation of CpG islands between patients, which is influenced by TET2 and DNMT3B. These findings demonstrate that ALL is characterized by an unusually highly methylated genome and provide further insights into the non-canonical regulation of methylation in cancer.
Factors influencing maternal microchimerism throughout infancy and its impact on infant T cell immunity
Authors: Christina Balle, Blair Armistead, Agano Kiravu, Xiaochang Song, Anna-Ursula Happel, Angela A. Hoffmann, Sami B. Kanaan, J. Lee Nelson, Clive M. Gray, Heather B. Jaspan, Whitney E. Harrington
Journal: Journal of Clinical Investigation (2022)

Determinants of the acquisition and maintenance of maternal microchimerism (MMc) during infancy and the impact of MMc on infant immune responses are unknown. We examined factors that influence MMc detection and level across infancy and the effect of MMc on T cell responses to bacillus Calmette-Guérin (BCG) vaccination in a cohort of HIV-exposed, uninfected and HIV-unexposed infants in South Africa. MMc was measured in whole blood from 58 infants using a panel of quantitative PCR assays at day 1, and 7, 15, and 36 weeks of life. Infants received BCG at birth, and selected whole blood samples from infancy were stimulated in vitro with BCG and assessed for polyfunctional CD4+ T cell responses. MMc was present in most infants across infancy, with levels ranging from 0 to 1,193/100,000 genomic equivalents and was positively impacted by absence of maternal HIV, maternal and infant HLA compatibility, infant female sex, and exclusive breastfeeding. Initiation of maternal antiretroviral therapy prior to pregnancy partially restored MMc level in HIV-exposed, uninfected infants. Birth MMc was associated with an improved polyfunctional CD4+ T cell response to BCG. These data emphasize that both maternal and infant factors influence the level of MMc, which may subsequently affect infant T cell responses.
Extracellular vesicles: Emerging tools as therapeutic agent carriers
Authors: Shan Liu, Xue Wu, Sutapa Chandra, Christopher Lyon, Bo Ning, Li jiang, Jia Fan, Tony Y. Hu
Journal: Acta Pharmaceutica Sinica B (2022)

Extracellular vesicles (EVs) are secreted by both eukaryotes and prokaryotes, and are present in all biological fluids of vertebrates, where they transfer DNA, RNA, proteins, lipids, and metabolites from donor to recipient cells in cell-to-cell communication. Some EV components can also indicate the type and biological status of their parent cells and serve as diagnostic targets for liquid biopsy. EVs can also natively carry or be modified to contain therapeutic agents (e.g., nucleic acids, proteins, polysaccharides, and small molecules) by physical, chemical, or bioengineering strategies. Due to their excellent biocompatibility and stability, EVs are ideal nanocarriers for bioactive ingredients to induce signal transduction, immunoregulation, or other therapeutic effects, which can be targeted to specific cell types. Herein, we review EV classification, intercellular communication, isolation, and characterization strategies as they apply to EV therapeutics. This review focuses on recent advances in EV applications as therapeutic carriers from in vitro research towards in vivo animal models and early clinical applications, using representative examples in the fields of cancer chemotherapeutic drug, cancer vaccine, infectious disease vaccines, regenerative medicine and gene therapy. Finally, we discuss current challenges for EV therapeutics and their future development.